The proposed research would continue studies of the epidemiology of non-insulin dependent diabetes mellitus (NIDDM) and genetic-environmental interaction in the etiology of NIDDM. The emergence of diabetes mellitus (DM) in Pacific and Indian Ocean islanders and certain ethnic groups in the USA has been concomitant with rapid socioeconomic and environmental changes. However, these may not be the only factors contributing to the increased rated of DM as there appear to be marked differences in susceptibility to NIDDM in different ethnic groups. The investigators propose to continue studies with 6 ethnic groups, i.e., Polynesians, Micronesians, Melanesians, Asian Indians, Chinese, and Creoles. They will pursue previously defined objectives involving longitudinal studies and will further analyze data already collected. Additional objectives have also been suggested by their recent progress. The longitudinal studies will focus on the island communities of Nauru, Western Samoa and Mauritius. The specific goals of the proposed research are as follows: 1. Define the occurrence and determinants of impaired glucose tolerance (IGT), NIDDM, and other cardiovascular disease risk factors, as well as the complications of DM in these populations; 2. Examine the natural history of IGT and NIDDM, including the role of hyperinsulinemia; 3. Assess whether specific genetic markers exist in subjects with NIDDM or at risk of NIDDM and whether any such factors operate similarly across ethnic groups; 4. Establish the role of extrinsic risk factors such as obesity, fat distribution, physical activity, diet, and parity in the etiology of NIDDM in these populations; 5. Examine environmental and genetic factors cross-sectionally and prospectively in relation to the development of micro- and macrovascular complications of NIDDM and mortality; 6. Extend data analysis to determine whether IGT and NIDDM are part of a non-communicable disease cluster, with hyperinsulinemia and/or insulin resistance as the primary defect; and 7. Pursue questions regarding the current classification and diagnostic criteria for DM. The principal investigator states the proposed research is significant for the population of the USA because (1) NIDDM is a significant problem which may be preventable and (2) elucidation of methods to detect "at risk" individuals, coupled with better understanding of the effects of environmental factors, could provide a framework for developing primary prevention programs for NIDDM (and possibly other non-communicable diseases) in the USA and other countries.